Complete ascertainment of cases of multiple intestinal polyposis and of colorectal cancer detected before age 40 years will be attempted for a 5-state mid-Atlantic area. Relatives, mainly first-degree, of ascertained cases will be investigated for benign or malignant tumors of the gastrointestinal tract and for extra-bowel tumors or other abnormalities. These persons will be placed in annual follow-up for longitudinal estimation of the cumulative risk of malignancy. Specific entities within these categories of familes -- e.g., familial polyposis of the colon, Peutz-Jeghers syndrome, Gardner syndrome, adenocarcinoma of colon and endometrium, juvenile polyposis of the colon etc.-- will be identified and the genetics of each studied (mutation rate, mode of inheritance, segregation ratio, linkage with marker traits). The chromosomes of colonic malignancies originating in multiple polyposis will be studied by methods comparable to those used for cervical cancer. The study will attempt to assess the relative merits of various diagnostic procedures. Colonoscopy will be the main method for study of the colon in relatives but will be supplemented by cytopathology of colonic washings, by barium enema both standard and air-contrast, and by standard histopathology (with EM in longitudinal study of selected cases). (CEA will be tested periodically by several methods in different laboratories.) The mechanics and nature of optimum follow-up of relatives at risk will be determined.